The proposed Program uses approaches within the disciplines of neuroanatomy, neuropharmacology, and neurophysiology to study a) factors that confer susceptibility to epileptogenesis in immature neocortex; b) electrophysiological abnormalities in injured neurons from hyperexcitable partially isolated neocortex; c) excitatory neurotransmission in developing and injured neocortex; d) changes in membrane and synaptic events in dentate gyrus following kindling; and e) noradrenergic disinhibition in hippocampal neurons. The specific projects are: I: Regulation of Neuronal Excitability and Epileptogenesis; II: Changes in Neuronal Excitability During Kindling-Induced Epilepsy; III: Regulation of Neuronal Excitability by Norepinephrine; and IV. Development of Excitatory Synaptic Transmission in Cortex. The techniques employed include intracellular current clamp and single electrode voltage clamp recordings; applications of patch clamp techniques to mature and immature neurons in in vitro slices for recording spontaneous and evoked synaptic currents and single channel activities; intracellular and retrograde neuronal labelling; applications of neurotransmitter agonists and antagonists to neurons; and induction of chronic hyperexcitability through kindling and creation of partially isolated cortical areas. The long-term goals of the Program are to obtain information which will provide a better understanding of the pathogenesis of epilepsy and insights which will lead to the development of rational new approaches to the prevention and treatment of this disorder. The studies outlined will also contribute to our understanding of normal regulation of cerebral excitability through effects of functional connections, specific transmitter systems, and intrinsic neuronal properties.